PT  - JOURNAL ARTICLE
AU  - Chao Yi
AU  - Tim WGM Spitters
AU  - Ezz Al-Din Ahmed Al-Far
AU  - Sen Wang
AU  - Tian Long Xiong
AU  - Simian Cai
AU  - Xin Yan
AU  - Kaomei Guan
AU  - Michael Wagner
AU  - Ali El-Armouche
AU  - Christopher L. Antos
TI  - A calcineurin-mediated scaling mechanism that controls a K<sup>+</sup>-leak channel to regulate morphogen and growth factor transcription
AID  - 10.1101/2020.07.03.186403
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2020.07.03.186403
4099  - http://biorxiv.org/content/early/2021/04/07/2020.07.03.186403.short
4100  - http://biorxiv.org/content/early/2021/04/07/2020.07.03.186403.full
AB  - The increase in activity of the two-pore potassium-leak channel Kcnk5b maintains allometric juvenile growth of adult zebrafish appendages. However, it remains unknown how this channel maintains allometric growth and how its bioelectric activity is regulated to scale these anatomical structures. We show the activation of Kcnk5b is sufficient to activate several genes that are part of important development programs. We provide in vivo transplantation evidence that the activation of gene transcription is cell autonomous. We also show that Kcnk5b will induce the expression of different subsets of the tested developmental genes in different cultured mammalian cell lines, which may explain how one electrophysiological stimulus can coordinately regulate the allometric growth of diverse populations of cells in the fin that use different developmental signals. We also provide evidence that the post-translational modification of serine 345 in Kcnk5b by calcineurin regulates channel activity to scale the fin. Thus, we show how an endogenous bioelectric mechanism can be regulated to promote coordinated developmental signaling to generate and scale a vertebrate appendage.Competing Interest StatementThe authors have declared no competing interest.